The role of specific central amygdala neurons in emotionally-triggered cataplexy
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Narcolepsy is a neurological disorder characterized by a person’s inability to regulate sleep-wake cycles. Excessive daytime sleepiness and cataplexy are prominent symptoms of narcolepsy. Cataplexy is partial to full body muscle atonia usually brought on by the person with narcolepsy experiencing a positive emotion. Some features of cataplexy resemble those of REM sleep, including similar brain activity and muscle atonia. The neuronal circuit that produces cataplexy has yet to be determined. The similarities between REM sleep and cataplexy support the hypothesis that cataplexy is the result of the REM atonia pathways being activated. An emotion processing region, the central amygdala (CeA), projects to known REM regulatory regions and plays a role in cataplexy. GABAergic neurons of the CeA are sufficient and necessary to trigger cataplexy in mice and project to brainstem regions that regulate muscle tone. Cataplexy is often triggered in a social setting, such as when seeing an old friend or telling a joke. Oxytocin (OT) is involved in many social behaviors, making it a viable link between social stimuli and cataplexy. We hypothesized that oxytocin receptor (OTR) neurons of the CeA, a sub-population of GABAergic neurons, promote emotionally-triggered cataplexy. To determine the social phenotype of the narcolepsy mouse model, the orexin knock-out (OXKO) mouse, we used established behavioral assays of social interaction and social memory. To determine if social reunification influenced the amount of cataplexy, group-housed OXKO mice were isolated for a short time and reunited with their littermates. To determine if OTR neurons of the CeA were sufficient and necessary to promote socially-triggered cataplexy, we used chemogenetic technology known as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to selectively activate or inhibit these neurons. We injected adeno-associated viral vectors coding for either the excitatory hM3 Cre-dependent DREADD or the inhibitory hM4 Cre-dependent DREADD into the CeA of orexin knock-out mice crossed with OTR-Cre mice, allowing for expression of the DREADD exclusively in the OTR neurons of the CeA. After injection with either saline or clozapine-N-oxide (CNO) we put the mice through a behavioral assay to see if emotionally-triggered cataplexy increased or decreased following the activation or inhibition of OTR neurons of the CeA. The behavioral assays showed that acute social interactions in OXKO is normal, however they do have a social memory impairment. In addition, reunification promotes cataplexy in most OXKO mice. With the chemogenetic experiments, our number of mice is too low to report if OTR neurons of the CeA are sufficient and/or necessary for cataplexy at this time.
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